title: Chondrogenic differentiation of adipose-derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix.
abstract: Adipose-derived adult stem cells (ASCs) have the ability to differentiate into a chondrogenic phenotype in response to specific environmental signals such as growth factors or artificial biomaterial scaffolds. In this study, we examined the hypothesis that a porous scaffold derived exclusively from articular cartilage can induce chondrogenesis of ASCs. Human ASCs were seeded on porous scaffolds derived from adult porcine articular cartilage and cultured in standard medium without exogenous growth factors. Chondrogenesis of ASCs seeded within the scaffold was evident by quantitative RT-PCR analysis for cartilage-specific extracellular matrix (ECM) genes. Histological and immunohistochemical examination showed abundant production of cartilage-specific ECM components-particularly, type II collagen-after 4 or 6 weeks of culture. After 6 weeks of culture, the cellular morphology in the ASC-seeded constructs resembled those in native articular cartilage tissue, with rounded cells residing in the glycosaminoglycan-rich regions of the scaffolds. Biphasic mechanical testing showed that the aggregate modulus of the ASC-seeded constructs increased over time, reaching 150 kPa by day 42, more than threefold higher than that of the unseeded controls. These results suggest that a porous scaffold derived from articular cartilage has the ability to induce chondrogenic differentiation of ASCs without exogenous growth factors, with significant synthesis and accumulation of ECM macromolecules, and the development of mechanical properties approaching those of native cartilage. These findings support the potential for a processed cartilage ECM as a biomaterial scaffold for cartilage tissue engineering. Additional in vivo evaluation is necessary to fully recognize the clinical implication of these observations.
authors.affiliation: Departments of Surgery and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Nai-Chen
authors.initials: NC
authors.lastname: Cheng
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Estes
authors.forename: Hani A
authors.initials: HA
authors.lastname: Awad
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation; D020219:Chondrogenesis; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010539:Permeability; D016062:Porosity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen; D004247:DNA